FIELD OF THE INVENTION
The present invention consists in a new non-therapeutic use of L-carnitine, alkanoyl L-carnitines and their pharmacologically acceptable salts as preservative agents for blood transfusions.
The present invention also consists in new stabilizing solutions for the storage of blood containing L-carnitine, alkanoyl L-carnitines or their pharmacologically acceptable salts.
What is meant by alkanoyl L-carnitines are acetyl, propionyl, butyryl, isobutyryl, valeryl and isovaleryl L-carnitine. Hereinafter, for reasons of simplicity, we shall refer only to L-carnitine, in the understanding, however, that the description also applies to the above-mentioned alkanoyl L-carnitines and their pharmacologically acceptable salts.
As is well known, L-carnitine is necessary for the translocation of fatty acids within the mitichondria where beta-oxidation takes place.
Various uses of L-carnitine are known, but all of these are of a therapeutic nature. For instance, L-carnitine is used in the cardiovascular field for the treatment of acute and chronic myocardial ischaemia, angina pectoris, heart failure and cardiac arrhythmias.
In the nephrological field, L-carnitine is administered to chronic uraemics undergoing regular haemodialytic treatment to combat myasthenia and the onset of muscular cramps.
Other therapeutic uses have to do with the normalization of the HDL:LDL+VLDL ratio and total parenteral nutrition. There is, however, no relationship between the known therapeutic uses of L-carnitine mentioned previously and the use envisaged in the present invention.
It is well known that the essential factors for good storage of blood in the liquid state are the temperature and the composition of the stabilizing solution.
The temperature must be such as to allow a reduction of the metabolic activity of the erythrocytes without damaging them. The optimal temperature is 4.degree. C. .+-.2.degree. C.
The stabilizing solutions must be able to make the blood unclottable, to reduce the glycolytic activity of the red blood cells and, at the same time, permit such activity by providing an adequate substrate.
The efficacy of a stabilizing solution is assessed by observing both the alterations arising in the erythrocytes in vitro and their survival in vivo, after variable periods of storage at optimal temperature.
The alterations to the erythrocytes in vitro can be checked by evaluating the amount of haemoglobin released by the erythrocytes, their osomotic and mechanical fragility, the changes in their shape and volume and the chemical changes they undergo.
The stabilizing solutions used to date do not allow good storage of blood for more than 14 to 21 days.
For instance, if the blood is collected in ACD (citric acid-sodium citrate-dextrose), one of the most widely used stabilizing solutions in the past, and transfused after 14 or 21 days of storage, the in-vivo survival rates of erythrocytes 24 h after transfusion are 90 and 80%, respectively; it is also well known that the red blood cells that remain in circulation 24 h after transfusion have a survival rate equal to that of fresh blood.
During storage, erythrocytes undergo alterations with formation of spherocytes and burr cells. The erythrocytes swell and lose potassium and haemoglobin, which then increases in the plasma. At the same time there is a reduction in 2,3-DPG (2,3-diphosphoglycerate) and thus an increase in the affinity of haemoglobin for oxygen, which is released to tissues in smaller amounts.
The alterations of erythrocytes stored in ACD may be at least partly corrected by adding phosphate to the stabilizing solution. Thus CPD (citrate-phsophate-dextrose) solutions have come to be used for the storage of blood and are now the ones most commonly employed. The addition of phosphate gives rise to the maintenance of a higher level of 2,3-DPG and thus a lower affinity of haemoglobin for oxygen. However, the in-vivo survival of erythrocytes stored in CPD is little better, if not indeed identical to that of erythrocytes stored in ACD.